title: Using biomarkers to predict progression from clinically isolated syndrome to multiple sclerosis.
abstract: BACKGROUND
  Detection of brain lesions disseminated in space and time by magnetic resonance imaging remains a cornerstone for the diagnosis of clinically definite multiple sclerosis. We have sought to determine if gene expression biomarkers could contribute to the clinical diagnosis of multiple sclerosis.
  
  
  METHODS
  We employed expression levels of 30 genes in blood from 199 subjects with multiple sclerosis, 203 subjects with other neurologic disorders, and 114 healthy control subjects to train ratioscore and support vector machine algorithms. Blood samples were obtained from 46 subjects coincident with clinically isolated syndrome who progressed to clinically definite multiple sclerosis determined by conventional methods. Gene expression levels from these subjects were inputted into ratioscore and support vector machine algorithms to determine if these methods also predicted that these subjects would develop multiple sclerosis. Standard calculations of sensitivity and specificity were employed to determine accuracy of these predictions.
  
  
  RESULTS
  Our results demonstrate that ratioscore and support vector machine methods employing input gene transcript levels in blood can accurately identify subjects with clinically isolated syndrome that will progress to multiple sclerosis.
  
  
  CONCLUSIONS
  We conclude these approaches may be useful to predict progression from clinically isolated syndrome to multiple sclerosis.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine, MCN T3219, 1161 21st Avenue South, Nashville, TN, 37232-2681, USA. tom.aune@vanderbilt.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Tossberg
authors.forename: Philip S
authors.initials: PS
authors.lastname: Crooke
authors.forename: Melodie A
authors.initials: MA
authors.lastname: Henderson
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Sriram
authors.forename: Davit
authors.initials: D
authors.lastname: Mrelashvili
authors.forename: Saskia
authors.initials: S
authors.lastname: Vosslamber
authors.forename: Cor L
authors.initials: CL
authors.lastname: Verweij
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Olsen
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Aune